Caffeine is a widely used neurostimulant that is found in many foods and beverages such as coffee, tea, soft drinks, and chocolate. Its high incidence of use is significant because caffeine has both acute and chronic effects on measures of mood, cognitive performance, and physiology. Caffeine nonselectively antagonizes adenosine receptors, thereby acting as both a neurostimulant and vasoconstrictor. Acutely, caffeine improves mood and attention, and reduces resting cerebral blood flow. However, chronic caffeine use results in an upregulation of adenosine receptors. Among chronic users there is evidence that tolerance develops to the neurostimulant effects, and withdrawal symptoms such as headache and fatigue appear during caffeine abstinence. In fact, it has been proposed the reversal of the withdrawal effects outweighs any acute net benefits of caffeine in chronic users. This proposal has been debated because discrepancies exist in the behavioral literature and a more comprehensive investigation of the effects of caffeine and caffeine withdrawal is warranted. Recently, the effects of caffeine have been studied using functional magnetic resonance imaging (fMRI). However, by antagonizing vascular adenosine receptors, caffeine interferes with the coupling between neural activity and the hemodynamic response. This may reduce the peak amplitude of the blood oxygenation level dependent (BOLD) signal, inconsistent with the neurostimulant effects of caffeine. This issue may be avoided by measuring time course parameters of the BOLD signal instead, since evidence suggests that caffeine decreases the latency of a neural response to a stimulus. The proposed study will address this by utilizing measures of mood, cognitive performance, and physiology to investigate the effects of caffeine in a native caffeinated state and a withdrawal state following 30 hours of caffeine abstinence. The specific aims for this project will determine the state and drug effects on 1) measures of mood and cognitive performance, 2) time course parameters of the BOLD signal, and 3) the relationship between behavioral performance and time course parameters of the BOLD signal. PUBLIC HEALTH RELEVANCE: Caffeine is an excellent model drug because it is safe to administer and has a low abuse liability, yet chronic use will result in tolerance and withdrawal symptoms similar to drugs of abuse. As a model drug, caffeine could add to our understanding of how the avoidance of withdrawal symptoms contributes to the reinforcing effects of drugs. The issues addressed in this proposed study are pertinent to all neuroactive drugs that simultaneously affect cerebral blood flow. The information gained from this study will improve our understanding of caffeine and will lend itself to the study of other drugs using pharmacological fMRI.